We propose prioritization of prostate cancer patients to PD-L1 checkpoint therapy by assessing activity of IFN-gamma/PD-L1 signaling in tumor from transcriptional profile. To this end, we introduced a new approach for inferring pathway activity and suppression (IPAS) by assessing significance of positioning pathway's genes expression levels at top (activation) or bottom (suppression) in gene expression profile of a given tumor. By ordering tumors along IFN-gamma-PD-L1 axis, we determined distinct "IFN-gamma-depleted" and "IFN-gamma-enriched" immune subtypes, genes involved in immune evasion and potential targets for combination therapy. Using IPAS scoring method, we proposed biomarker panels for accurate ranking tumors along IFN-gamma/PD-L1 axis.

中文翻译：

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通过沿IFN-γ轴对肿瘤进行排名并确定免疫抵抗机制，将前列腺癌优先于免疫检查点治疗

通过从转录谱评估肿瘤中IFN-γ/ PD-L1信号的活性，我们建议将前列腺癌患者优先用于PD-L1检查点治疗。为此，我们通过评估给定肿瘤的基因表达谱中顶部（激活）或底部（抑制）的定位途径的基因表达水平的重要性，引入了一种推断途径活性和抑制（IPAS）的新方法。通过沿IFN-γ-PD-L1轴排列肿瘤，我们确定了独特的“IFN-γ耗尽”和“IFN-γ富集”免疫亚型，涉及免疫逃逸的基因以及联合治疗的潜在靶标。使用IPAS评分方法，我们提出了生物标志物组，用于沿IFN-γ/ PD-L1轴对肿瘤进行准确排名。